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Biomedical subjects

Amit Patel

Publications and source records attributed to Amit Patel.

18 recordsLinked to original sources
PubMed2025

Prevalence and predictors of low bone mineral density in pediatric inflammatory bowel disease.

OBJECTIVES: Bone health is at risk in children with inflammatory bowel disease (IBD). This study examined the prevalence and predictors of low bone mineral density (BMD) in a cohort of children and young adults with IBD. METHODS: This single-center retrospective study included patients with IBD, ages 3.5-22 years, with completed dual x-ray absorptiometry (DXA) scans from 2006 to 2019. Demographic, clinical, and laboratory data were collected. Logistic regression analysis identified predictors associated with low BMD (Z-scores&#x2009;&#x2264;&#x2009;-2 standard deviations [SDs]) for three outcomes. In an overlapping IBD cohort with available genetic data between 2002 and 2019 (n&#x2009;=&#x2009;378), genetic risk for diminished bone health was calculated using published polygenic risk scores generated from genome-wide association studies based on DXA or heel ultrasound speed of sound (SOS). Linear regression analysis examined associations of low BMD and genetic risk. RESULTS: Low BMD prevalence was 7% in our cohort (n&#x2009;=&#x2009;600) based on spine bone mineral apparent density (BMAD), which best accounts for growth delays. Median (interquartile range [IQR]) spine BMAD Z-score was -0.37&#x2009;SD (-1.11 to 0.35). Predictors of low BMAD included lower BMI Z-score (odds ratio [OR]: 0.67, p value: 0.02) and decreased height Z-score (OR: 0.6, p value: 0.005). Of those with longitudinal data (n&#x2009;=&#x2009;118), low BMI (OR: 0.44, p value: <0.001) and steroid use (OR: 3.42, p value: 0.01) were associated with suboptimal bone health (Z-scores&#x2009;&#x2264;&#x2009;-1SD). In the cohort with genetic data, heel genomic SOS (&#x3b2; [standard error] = 0.17 [0.35], p&#x2009;&#x2264;&#x2009;0.01) was associated with BMD. CONCLUSIONS: Lower BMI should prompt DXA monitoring in pediatric IBD. Genetic predisposition may identify an at-risk subpopulation.

Humans↗
PubMed2006

Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands.

The liver X receptors (LXRs) are ligand-activated transcription factors that regulate the expression of genes controlling lipid metabolism. Oxysterols bind LXRs with high affinity in vitro and are implicated as ligands for the receptor. We showed previously that accumulation of selected dietary sterols, in particular stigmasterol, is associated with activation of LXR in vivo. In the course of the defining of structural features of stigmasterol that confer LXR agonist activity, we determined that the presence of an unsaturated bond in the side chain of the sterol was necessary and sufficient for activity, with the C-24 unsaturated cholesterol precursor sterols desmosterol and zymosterol exerting the largest effects. Desmosterol failed to increase expression of the LXR target gene, ABCA1, in LXRalpha/beta-deficient mouse fibroblasts, but was fully active in cells lacking cholesterol 24-, 25-, and 27-hydroxylase; thus, the effect of desmosterol was LXR-dependent and did not require conversion to a side chain oxysterol. Desmosterol bound to purified LXRalpha and LXRbeta in vitro and supported the recruitment of steroid receptor coactivator 1. Desmosterol also inhibited processing of the sterol response element-binding protein-2 and reduced expression of hydroxymethylglutaryl-CoA reductase. These observations are consistent with specific intermediates in the cholesterol biosynthetic pathway regulating lipid homeostasis through both the LXR and sterol response element-binding protein pathways.

ATP Binding Cassette Transporter 1↗
PubMed2006

Saturation technique does not improve cancer detection as an initial prostate biopsy strategy.

PURPOSE: We reported on the results of a sequential cohort study comparing office based saturation prostate biopsy to traditional 10-core sampling as an initial biopsy. MATERIALS AND METHODS: Based on improved cancer detection of office based saturation prostate biopsy repeat biopsy, we adopted the technique as an initial biopsy strategy to improve cancer detection. Two surgeons performed 24-core saturation prostate biopsies in 139 patients undergoing initial biopsy under periprostatic local anesthesia. Indication for biopsy was an increased PSA of 2.5 ng/dl or greater in all patients. Results were compared to those of 87 patients who had previously undergone 10-core initial biopsies. RESULTS: Cancer was detected in 62 of 139 patients (44.6%) who underwent saturation biopsy and in 45 of 87 patients (51.7%) who underwent 10-core biopsy (p >0.9). Breakdown by PSA level failed to show benefit to the saturation technique for any degree PSA increase. Men with PSA 2.5 to 9.9 ng/dl were found to have cancer in 53 of 122 (43.4%) saturation biopsies and 26 of 58 (44.8%) 10-core biopsies. Complications included 3 cases of prostatitis in each group. Rectal bleeding was troublesome enough to require evaluation only in 3 men in the saturation group and 1 in the 10-core group. CONCLUSIONS: Although saturation prostate biopsy improves cancer detection in men with suspicion of cancer following a negative biopsy, it does not appear to offer benefit as an initial biopsy technique. These findings suggest that further efforts at extended biopsy strategies beyond 10 to 12 cores are not appropriate as an initial biopsy strategy.

Adult↗
PubMed2006

Host protein interactions with enteropathogenic Escherichia coli (EPEC): 14-3-3tau binds Tir and has a role in EPEC-induced actin polymerization.

Enteropathogenic Escherichia coli (EPEC) cause infantile diarrhoea and are characterized by their ability to produce attaching and effacing lesions on the surface of intestinal epithelial cells. EPEC employ a filamentous type III secretion system to deliver effector molecules that subvert mammalian cell function to generate actin- and cytokeratin-rich pedestals beneath adherent bacteria. Tir is a major effector protein that is delivered to the plasma membrane of the eukaryotic cell where it acts as the receptor for the bacterial adhesin intimin. Host cell proteins that are recruited to the site of intimate attachment include focal adhesion and cytoskeletal proteins that contribute to pedestal formation. We have used Tir as bait in a yeast two-hybrid screen to identify the protein 14-3-3tau as a binding partner. 14-3-3 proteins are a family of adaptor proteins that modulate protein function in all eukaryotic cells. Here we demonstrate that the tau isoform (also known as theta) of 14-3-3 can bind specifically to Tir in a phosphorylation-independent manner, and that the interaction occurs during the infection process by co-immunoprecipitation of the partners from infected HeLa cell extracts. 14-3-3tau is recruited to the site of the pedestal (3 h after infection) and can decorate attached EPEC in the later stages of the infection process (5-7 h). Pedestal formation can be impaired by depletion of cellular 14-3-3tau using small interfering RNAs. This study indicates a direct functional role for the 14-3-3tau:Tir interaction and is the first to demonstrate the association of a host protein with the surface of EPEC.

14-3-3 Proteins↗
PubMed2006

EspF of enteropathogenic Escherichia coli binds sorting nexin 9.

EspF of enteropathogenic Escherichia coli targets mitochondria and subverts a number of cellular functions. EspF consists of six putative Src homology 3 (SH3) domain binding motifs. In this study we identified sorting nexin 9 (SNX9) as a host cell EspF binding partner protein, which binds EspF via its amino-terminal SH3 region. Coimmunoprecipitation and confocal microscopy showed specific EspF-SNX9 interaction and non-mitochondrial protein colocalization in infected epithelial cells.

Amino Acid Motifs↗
PubMed2005

Unattended home sleep studies for the evaluation of suspected obstructive sleep apnoea syndrome in children.

Children suspected of obstructive sleep apnoea syndrome (OSAS) are traditionally investigated in hospital with overnight sleep studies, and single-channel pulse oximetry is the commonest form of initial study. A prospective study was conducted comparing unsupervised sleep studies, using a Nellcor N-395 pulse oximeter, performed in hospital and at home. Two hundred and eleven patient studies were completed in 18 months, 158 in hospital and 53 at home. The median age of patients was four years in both groups. The mean study duration was 9 h 5 min in hospital and 9 h 12 min at home (P = 0.75). The mean time in pulse search was 0.4% (SD = 0.7) in hospital and 0.2% (SD = 0.4) at home (P = 0.008). The number of failed studies was 96 of 254 (38%) in hospital and three of 56 (5%) at home (P < 0.001). Overall, 149 hospital bed days were saved (at pounds 690 per bed day), representing pounds 68,540 saved annually. The results show that unattended home sleep studies in the form of overnight pulse oximetry can be performed to a standard better than hospital studies, where local community nursing facilities exist.

Child, Preschool↗
PubMed2004

Involvement of the intermediate filament protein cytokeratin-18 in actin pedestal formation during EPEC infection.

While remaining extracellular, enteropathogenic Escherichia coli (EPEC) establish direct links with the cytoskeleton of the target epithelial cell leading to the formation of actin-rich pedestals underneath attached bacteria. The translocated adaptor protein Tir forms the transmembrane bridge between the cytoskeleton and the bacterium; the extracellular domain of Tir functions as a receptor for the bacterial adhesin intimin, while the intracellular amino and carboxy termini interact with a number of focal adhesion and other cytoskeletal proteins; and recruitment of some is dependent on phosphorylation of Tyr 474. Using Tir as bait and HeLa cell cDNA library as prey in a yeast two-hybrid screen, we identified cytokeratin 18 as a novel Tir partner protein. Cytokeratin 18 is recruited to the EPEC-induced pedestal and has a direct role in actin accretion and cytoskeleton reorganization. This study is the first to implicate intermediate filaments in microfilament reorganization following EPEC infection.

Actins↗
PubMed2004

Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells.

We completed a multicenter study of the effects of pomegranate cold-pressed (Oil) or supercritical CO(2)-extracted (S) seed oil, fermented juice polyphenols (W), and pericarp polyphenols (P) on human prostate cancer cell xenograft growth in vivo, and/or proliferation, cell cycle distribution, apoptosis, gene expression, and invasion across Matrigel, in vitro. Oil, W, and P each acutely inhibited in vitro proliferation of LNCaP, PC-3, and DU 145 human cancer cell lines. The dose of P required to inhibit cell proliferation of the prostate cancer cell line LNCaP by 50% (ED(50)) was 70 microg/mL, whereas normal prostate epithelial cells (hPrEC) were significantly less affected (ED(50) = 250 g/mL). These effects were mediated by changes in both cell cycle distribution and induction of apoptosis. For example, the androgen-independent cell line DU 145 showed a significant increase from 11% to 22% in G(2)/M cells (P <.05) by treatment with Oil (35 microg/mL) with a modest induction of apoptosis. In other cell lines/treatments, the apoptotic response predominated, for example, in PC-3 cells treated with P, at least partially through a caspase 3-mediated pathway. These cellular effects coincided with rapid changes in mRNA levels of gene targets. Thus, 4-hour treatment of DU 145 cells with Oil (35 microg/mL) resulted in significant 2.3 +/- 0.001-fold (mean +/- SEM) up-regulation of the cyclin-dependent kinase inhibitor p21((waf1/cip1)) (P <.01) and 0.6 +/- 0.14-fold down-regulation of c-myc (P <.05). In parallel, all agents potently suppressed PC-3 invasion through Matrigel, and furthermore P and S demonstrated potent inhibition of PC-3 xenograft growth in athymic mice. Overall, this study demonstrates significant antitumor activity of pomegranate-derived materials against human prostate cancer.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Prostate cancer detection with office based saturation biopsy in a repeat biopsy population.

PURPOSE: Patients at increased risk for prostate cancer with previously negative biopsies pose a diagnostic challenge. We have previously demonstrated that extensive saturation biopsy can be performed in an office setting. We now report the diagnostic yield of office saturation biopsy in patients at increased risk for prostate cancer and at least 1 negative prior biopsy. MATERIALS AND METHODS: We performed saturation prostate biopsy with local anesthesia in the office in 116 patients with at least 1 prior negative biopsy and with certain risk factors, namely persistently elevated prostate specific antigen, abnormal digital rectal examination, or prior atypia or PIN on prior biopsy. RESULTS: A total of 34 cancers were detected for an overall diagnostic yield of 29%. A 64% detection rate was noted when a patient had undergone a single prior sextant biopsy. Subgroup analysis revealed a cancer detection rate of 41% when only prior sextant biopsies were performed, and a 24% detection rate when 10 or more cores were taken on prior biopsy. The detection rate was 33% when only 1 prior biopsy was taken and it was 24% when 2 or more prior biopsies were performed. CONCLUSIONS: Saturation biopsy can be performed safely and effectively in the office with a significant diagnostic yield even in patients with previous extended biopsy schemes. We believe that it should be the next diagnostic step after an initial negative biopsy in patients in whom the diagnosis of prostate cancer is strongly suspected.

Aged↗
PubMed2003

3-alkoxy-5-isoxazolidinones mimic beta-lactams.

3-Alkoxy-5-isoxazolidinones mimic the action of beta-lactams. They bind to the penicillin-binding proteins. They inhibit Class A, Class B, and Class D beta-lactams. They inhibit the growth of Bacillus subtilis. We give a novel synthesis for these compounds.

Anti-Bacterial Agents↗
PubMed2003

Thoracic Outlet Syndromes.

The clinical presentation of thoracic outlet syndrome depends on which anatomic structure is compressed in the area of the thoracic outlet (eg, the axillary-subclavian artery, vein, brachial plexus, or the sympathetic nerves). The clinical syndrome may be isolated to one or a mixture of these compressed anatomic structures. Although there are multiple compressive forces, the first rib is the common denominator, and extirpation of this structure is the "gold" standard for therapy. The various syndromes are discussed in their clinical order of frequency. For severe nerve compression, whether upper or lower brachial plexus, the best surgical procedure is the transaxillary first rib resection, anterior scalenectomy, and neurovascular decompression. Axillary-subclavian vein occlusion (ie, Paget-Schroetter syndrome) is best treated with early diagnosis, intravenous thrombolysis of the clot, transaxillary first rib resection anterior scalenectomy, and resection of the costoclavicular ligament. Arterial compression, occlusion, or aneurysm may occur with or without peripheral emboli and require a supraclavicular approach with arterial ligation, endarterectomy, or bypass grafts from the supraclavicular subclavian to the infraclavicular brachial artery. Compression of the sympathetic nerves produces vasospasm, Raynaud's phenomenon, or Raynaud's disease, requiring dorsal sympathectomy as well as first rib extirpation occasionally. This may be performed through the transaxillary, supraclavicular posterior, or thoracoscopic approach. Recurrent thoracic outlet syndrome may involve any or all of the above anatomic syndromes. The surgical approach is best from the posterior, high thoracoplasty, muscle-splitting incision, performing neurolysis of the C7, C8, and T1 nerve roots and the brachial plexus as well as release of any vascular constriction.

Journal Article↗
PubMed2003

Effect of 0.5 Tesla magnetic resonance imaging on the surgical management of breast cancer patients.

BACKGROUND: This trial examines the utility of breast magnetic resonance imaging (MRI) for detection of occult breast disease and its effect on surgical treatment. METHODS: Between October 2000 and March 2002, 76 of 1289 patients underwent bilateral breast MRI within 4 months of a mammogram. The MRI scan, mammogram, pathology reports, and physicians' notes were reviewed to determine impact of MRI on surgical treatment. RESULTS: Magnetic resonance imaging detected 23 additional lesions in 19 patients not detected by mammogram. Cancer occult to mammography was detected by MRI in 6 women, constituting 7.9%. Magnetic resonance imaging impacted surgical treatment plans in 10 of 76 (13.2%) patients. CONCLUSIONS: Magnetic resonance imaging is effective at identifying new subclinical breast disease not seen on mammography. Ten of 76 patients (13.2%) who underwent MRI had their surgical management altered due to MRI findings. Specific criteria should be studied to know which subgroups would benefit most from breast MRI.

Adult↗
PubMed2002

Activation of the transcription factor NF-kappaB by Campylobacter jejuni.

Campylobacter jejuni is a food-borne pathogen responsible for infectious enterocolitis. The early-response transcription factor NF-kappa B triggers the expression of genes associated with cellular immune and inflammatory responses. Co-incubation of HeLa cells with viable C. jejuni leads to the activation of the transcription factor NF-kappa B as determined by specific induction of a cellular luciferase-based reporter. Boiled cell-free extracts of C. jejuni are also potent dose-dependent stimulators of NF-kappa B-dependent transcription, the levels of which can reach up to 1000-fold as compared with independent controls. Using both cultured HeLa cells and human colonic epithelial (HCA-7) cells, the activation of NF-kappa B by C. jejuni boiled extract has been monitored through the degradation of IKB alpha and DNA binding of the nuclear translocated p50/p65 heterodimer of NF-kappa B. These events are co-ordinated with elaboration of the pro-inflammatory cytokine interleukin-8. Fractionation of the boiled C. jejuni extract suggests that the majority of the bioactive component has a molecular mass of 3 kDa or less, which is insensitive to proteinase K treatment.

Blotting, Western↗
PubMed2002

Circadian variation in cell-adhesion molecule expression by normal human leukocytes.

Adhesion molecules located on the surface of blood-borne leukocytes permit adherence of leukocytes to the microvascular endothelium, diapedesis of leukocytes across vessel walls, formation of intimate multicell interactions, and enhanced transmembrane signal transduction. Since some leukocyte-mediated immune functions exhibit nocturnal intensification, the current study was conducted to investigate the hypothesis that expression of selected cell adhesion molecules (CAM) varies with circadian periodicity. Blood was collected from normal human donors over a 24-h period and CAM expression by monocytes, neutrophils, and lymphocytes evaluated by monoclonal antibody binding and flow cytometry. All leukocyte classes exhibited significant circadian-like variation (p < 0.05) in CD62L (L-selectin) expression. Similarly, a diurnal variation (p < 0.05) in monocyte and neutrophil CD54 (ICAM-1) was observed. Finally, neutrophils demonstrated a circadian-like variation (p < 0.05) in CD11a (LFA-1a). The rhythmic alterations in CAM expression may be clinically relevant, since changes in CAM expression have the potential to modulate the leukocyte-induced pathogenesis associated with disease progressions such as nocturnal asthma, the nighttime exacerbations of rheumatoid arthritis, and the high nocturnal incidence of cerebrovascular and cardiovascular crisis.

Adult↗